A need for tritium labelled materials exists in many areas of research ranging from DNA studies to structure analysis. High concentrations of tritium, hence high specific activities, are generally required due to massive dilutions that occur with the use of these substances. Tritide reducing agents provide an attractive approach for the incorporation of tritium into molecules of biochemical interest. A number of reducing agents are under investigation in an effort to determine their selectivity and reducing power, as well as their ease of generation. Tributyltin hydride and tris(trimethylsilyl)-silane have been used to demonstrate selective dehalogenations of nitro-containing substrates. Free radical cyclizations and rearrangement reactions have been carried out using tributyltin hydride as well. Other potential tritiating agents that are being addressed in our program include diphenylsilane, zirconocene monochloride hydride, catecholborane, lithium aluminium hydride, lithium borohydride, lithium triethyl borohydride and a new reagent, lithium trimethoxy borohydride. Due to significant improvements in the reactivity of lithium hydride (a precursor to a number of these reagents), it was anticipated that this reagent might also have potential as an interesting reducing agent. A survey of the reactivity of lithium hydride and of lithium trimethoxy borohydride toward various functional groups was conducted and published over the last few years. Recently we have completed work on two important hydride systems. We have established a simple and efficient exchange process for labelling each of the alkali metal borohydrides, and have analyzed the labelled products by a combination of 1H, 2H, 3H, and 11B NMR techniques. We have found that the borohydrides can be exchanged to ca. 80% tritium content in a single exchange cycle. Conditions for use of the labelled borohydrides in exemplary reduction reactions were optimized. The generation of diborane from borohydride was also optimized, and the product characterized by NMR analysis. We have also carried this reagent through an exemplary reduction reaction, and fully characterized the labelled products. These reagents have become extremely important in support of our User, Core and our Collaborative research functions. In researching the production of tritiated diborane, it became clear that subtle modification of the reaction stoichiometry and conditions would yield LiBT4. In very short time this was confirmed, and the reagent was synthesized, characterized, and its use demonstrated in simple reductions. The importance and utility of this reagent was confirmed by the fact that it had been used in two User projects within a month of the proof-of-principle experiments. With the ability to readily prepare exchange labelled alkali metal borohydrides (ca. 80% tritium content), we have investigated the formation of useful derivatives. Two important reagents for biomedical applications are NaBT(OAc)3 and NaBT3CN. Using our traditional approach of demonstrating chemistry first with hydrogen, then deuterium, and finally tritium, we are in the final stages of confirming the facile synthesis and use of these reagents. As with many of these hydride reagents, the triacetoxyborotritide reagent has been an integral part of a Collaborative project well before a publication describing its preparation can be prepared. Work on the hydride projects was significantly delayed during 1996-1998 by demands in EH&S and waste operations. Over the next year we will pursue further synthetic and characterization studies of NaBT(OAc)3, NaBT3CN, and NaBT4. Successful preparation of these materials at maximum specific activity depends on the synthesis of NaT, which is more difficult than the preparation of LiT. The Na derivatives have never been prepared at high specific activity, so a detailed manuscript describing this work will be appropriate. We hope that other hydrides under investigation during the next twelve months will include L-selectride, alpine-borane, and similar stereoselective reagents. Since the field of tritiated hydride chemistry has developed rapidly over the past ten years, we will attempt preparation of a review. A very large proportion of the NTLF User, Core and Collaborative projects are now built upon the availability of these hydride reagents, invented or proved by NTLF experiments over the past decade. The progress of this project has far-reaching effects for other NTLF research.